Neural basis for successful encoding and retrieval of prospective memory

Prospective memory (PM) refers to memory for future intentions. Difference due to memory (Dm effect) is the difference in neural activity related to stimuli that were subsequently remembered or forgotten. Using event-related potentials (ERPs), the present study investigated the Dm effect for PM using a subsequent task-switching paradigm. The results showed that a Dm effect of ERP P150 was more positive-going for later PM hit trials than for later PM forgotten trials during 100–200 ms. This Dm effect may reflect the process for the production of future intention or the process for attention. Consistent with previously reported Dm effects of other types of memory, we found that the fbN2 (250–280 ms) and late positivity component (400–700 ms) were stronger in later PM hit trials than in forgotten trials. The fbN2 was evoked by Chinese characters. The late positivity component was related to the precise encoding process. In conclusion, because of the early P150, PM encoding appears to be somewhat different from previously identified Dm effects. However, further research is needed. Our findings reveal that Dm effects of PM share similar characteristics with known Dm effects of other types of episodic memory after the very early stage of neural processing.     

Auditory event-related potentials to the apparent auditory image motion

Auditory event-related potentials (ERP) were registered to the dichotically presented white noise stimuli (duration 1500 ms, band 150-1200 Hz). Abrupt or gradual change ofinteraural time difference in the middle of stimuli (750 ms after sound offset) was perceived as an apparent auditory image (AI) instant relocation or motion from the midline to one of the ears. In responses these stimuli two ERPs were observed: one to the sound onset, and second--to the onset of motion or AI relocation. ERPs to AI relocation differed from those to sound onset in longer components latencies (123 ms versus 105 ms for N 1,227 ms versus 190 ms for P2). In responses to AI motion component latencies were even longer (N1: 137 ms, P2: 240 ms); N1 amplitude was greater at sites contralateral to the AI motion direction.     

<Emphasis Type="Italic">In situ</Emphasis>detection of non-polyadenylated RNA molecules using Turtle Probes and target primed rolling circle PRINS

Background  

In situ detection is traditionally performed with long labeled probes often followed by a signal amplification step to enhance the labeling. Whilst short probes have several advantages over long probes (e.g. higher resolution and specificity) they carry fewer labels per molecule and therefore require higher amplification for detection. Furthermore, short probes relying only on hybridization for specificity can result in non-specific signals appearing anywhere the probe attaches to the target specimen. One way to obtain high amplification whilst minimizing the risk of false positivity is to use small circular probes (e.g. Padlock Probes) in combination with target primed rolling circle DNA synthesis. This has previously been used for DNA detection in situ, but not until now for RNA targets.     

Achieving the promise and avoiding the peril of chemical probes using genetics

Chemical probes can be valuable tools for studying protein targets, but addressing concerns about a probe's cellular target or its specificity can be challenging. A reliable strategy is to use a mutation that does not alter a target's function but confers resistance (or sensitizes) to the inhibitor in both cellular and biochemical assays. However, challenges remain in finding such mutations. Here, we discuss structure- and cell-based approaches to identify resistance- and sensitivity-conferring mutations. Further, we describe how resistance-conferring mutations can help with compound design, and the use of saturation mutagenesis to characterize a compound binding site. We highlight how genetic approaches can ensure the proper use of chemical inhibitors to pursue mechanistic studies and test therapeutic hypotheses.     

Attention Increases the Temporal Precision of Conscious Perception: Verifying the Neural-ST2 Model

What role does attention play in ensuring the temporal precision of visual perception? Behavioural studies have investigated feature selection and binding in time using fleeting sequences of stimuli in the Rapid Serial Visual Presentation (RSVP) paradigm, and found that temporal accuracy is reduced when attentional control is diminished. To reduce the efficacy of attentional deployment, these studies have employed the Attentional Blink (AB) phenomenon. In this article, we use electroencephalography (EEG) to directly investigate the temporal dynamics of conscious perception. Specifically, employing a combination of experimental analysis and neural network modelling, we test the hypothesis that the availability of attention reduces temporal jitter in the latency between a target''s visual onset and its consolidation into working memory. We perform time-frequency analysis on data from an AB study to compare the EEG trials underlying the P3 ERPs (Event-related Potential) evoked by targets seen outside vs. inside the AB time window. We find visual differences in phase-sorted ERPimages and statistical differences in the variance of the P3 phase distributions. These results argue for increased variation in the latency of conscious perception during the AB. This experimental analysis is complemented by a theoretical exploration of temporal attention and target processing. Using activation traces from the Neural-ST² model, we generate virtual ERPs and virtual ERPimages. These are compared to their human counterparts to propose an explanation of how target consolidation in the context of the AB influences the temporal variability of selective attention. The AB provides us with a suitable phenomenon with which to investigate the interplay between attention and perception. The combination of experimental and theoretical elucidation in this article contributes to converging evidence for the notion that the AB reflects a reduction in the temporal acuity of selective attention and the timeliness of perception.     

Effects of aging on event-related brain potentials (ERPs) in a visual detection task

Event-related brain potentials (ERPs) were recorded from 74 subjects (45 men) between 18 and 82 years of age in a simple visual detection task. On each trial the subject reported the location of a triangular flash of light presented briefly 20° laterally to the left or right visual field or to both fields simultaneously. ERPs to targets exhibited a similar morphology including P1, N1, P2, N2, and P3 components across all age groups. The principal effects of advancing age were (1) a marked reduction in amplitude of the posterior P1 component (75–150 latency) together with an amplitude increase of an anterior positivity at the same latency; (2) an increase in amplitude of the P3 component that was most prominent over frontal scalp areas; and (3) a linear increase in P3 peak latency. These results extend the findings of age-related changes in P3 peak latency and distribution to a non-oddball task in the visual modality and raise the possibility that short-latency ERPs may index changes in visual attention in the elderly.     

Mind perception: real but not artificial faces sustain neural activity beyond the N170/VPP

Faces are visual objects that hold special significance as the icons of other minds. Previous researchers using event-related potentials (ERPs) have found that faces are uniquely associated with an increased N170/vertex positive potential (VPP) and a more sustained frontal positivity. Here, we examined the processing of faces as objects vs. faces as cues to minds by contrasting images of faces possessing minds (human faces), faces lacking minds (doll faces), and non-face objects (i.e., clocks). Although both doll and human faces were associated with an increased N170/VPP from 175-200 ms following stimulus onset, only human faces were associated with a sustained positivity beyond 400 ms. Our data suggest that the N170/VPP reflects the object-based processing of faces, whether of dolls or humans; on the other hand, the later positivity appears to uniquely index the processing of human faces--which are more salient and convey information about identity and the presence of other minds.     

Effects of target length on the hybridization efficiency and specificity of rRNA-based oligonucleotide microarrays

The effect of target size on microarray hybridization efficiencies and specificity was investigated using a set of 166 oligonucleotide probes targeting the 16S rRNA gene of Escherichia coli. The targets included unfragmented native rRNA, fragmented rRNA ( approximately 20 to 100 bp), PCR amplicons (93 to 1,480 bp), and three synthetic single-stranded DNA oligonucleotides (45 to 56 bp). Fluorescence intensities of probes hybridized with targets were categorized into classes I (81 to 100% relative to the control probe), II (61 to 80%), III (41 to 60%), IV (21 to 40%), V (6 to 20%), and VI (0 to 5%). Good hybridization efficiency was defined for those probes conferring intensities in classes I to IV; those in classes V and VI were regarded as weak and false-negative signals, respectively. Using unfragmented native rRNA, 13.9% of the probes had fluorescence intensities in classes I to IV, whereas the majority (57.8%) exhibited false-negative signals. Similar trends were observed for the 1,480-bp PCR amplicon (6.6% of the probes were in classes I to IV). In contrast, after hybridization of fragmented rRNA, the percentage of probes in classes I to IV rose to 83.1%. Likewise, when DNA target sizes were reduced from 1,480 bp to 45 bp, this percentage increased approximately 14-fold. Overall, microarray hybridization efficiencies and specificity were improved with fragmented rRNA (20 to 100 bp), short PCR amplicons (<150 bp), and synthetic targets (45 to 56 bp). Such an understanding is important to the application of DNA microarray technology in microbial community studies.     

Does the perception of moving eyes trigger reflexive visual orienting in autism?

Does movement of the eyes in one or another direction function as an automatic attentional cue to a location of interest? Two experiments explored the directional movement of the eyes in a full face for speed of detection of an aftercoming location target in young people with autism and in control participants. Our aim was to investigate whether a low-level perceptual impairment underlies the delay in gaze following characteristic of autism. The participants'' task was to detect a target appearing on the left or right of the screen either 100 ms or 800 ms after a face cue appeared with eyes averting to the left or right. Despite instructions to ignore eye-movement in the face cue, people with autism and control adolescents were quicker to detect targets that had been preceded by an eye movement cue congruent with target location compared with targets preceded by an incongruent eye movement cue. The attention shifts are thought to be reflexive because the cue was to be ignored, and because the effect was found even when cue-target duration was short (100 ms). Because (experiment two) the effect persisted even when the face was inverted, it would seem that the direction of movement of eyes can provide a powerful (involuntary) cue to a location.     

Designing Driver Assistance Systems with Crossmodal Signals: Multisensory Integration Rules for Saccadic Reaction Times Apply

Modern driver assistance systems make increasing use of auditory and tactile signals in order to reduce the driver''s visual information load. This entails potential crossmodal interaction effects that need to be taken into account in designing an optimal system. Here we show that saccadic reaction times to visual targets (cockpit or outside mirror), presented in a driving simulator environment and accompanied by auditory or tactile accessories, follow some well-known spatiotemporal rules of multisensory integration, usually found under confined laboratory conditions. Auditory nontargets speed up reaction time by about 80 ms. The effect tends to be maximal when the nontarget is presented 50 ms before the target and when target and nontarget are spatially coincident. The effect of a tactile nontarget (vibrating steering wheel) was less pronounced and not spatially specific. It is shown that the average reaction times are well-described by the stochastic “time window of integration” model for multisensory integration developed by the authors. This two-stage model postulates that crossmodal interaction occurs only if the peripheral processes from the different sensory modalities terminate within a fixed temporal interval, and that the amount of crossmodal interaction manifests itself in an increase or decrease of second stage processing time. A qualitative test is consistent with the model prediction that the probability of interaction, but not the amount of crossmodal interaction, depends on target–nontarget onset asynchrony. A quantitative model fit yields estimates of individual participants'' parameters, including the size of the time window. Some consequences for the design of driver assistance systems are discussed.     

An ERP Study on Decisions between Attractive Females and Money

To investigate the neural processes of decision-makings between attractive females and money, we recorded 18 male participants'' brain event-related potentials (ERPs) when they performed a novel task of deciding between viewing an attractive female''s fuzzy picture in clear and gaining a certain amount of money. Two types of attractive females were included: sexy females and beautiful females. Several new electrophysiological discoveries were obtained as following. First, the beautiful females vs. money task (task B) elicited a larger positive ERP deflection (P2) than the sexy females vs. money task (task S) between 290 and 340 ms, and this probably related to the perception matching process between a visual input and an internal representation or expectation. Second, task S evoked greater negative ERP waves (N2) than task B during the time window of 340–390 ms, and this might relate to response conflict and cognitive monitoring for impulsive tendency. Third, the ERP positivity in task S was larger than task B in the time interval of 550–1000 ms, reflecting that sexy female images may have higher decision value for males than beautiful female images. Fourth, compared with choosing to gain money, choosing to view an attractive female evoked a larger late positive component (LPC) during the same time window, possibly because attractive females are more direct and evolutionarily earlier rewards for males than money amounts.     

From Mind to Mouth: Event Related Potentials of Sentence Production in Classic Galactosemia

Patients with classic galactosemia, an inborn error of metabolism, have speech and language production impairments. Past research primarily focused on speech (motor) problems, but these cannot solely explain the language impairments. Which specific deficits contribute to the impairments in language production is not yet known. Deficits in semantic and syntactic planning are plausible and require further investigation. In the present study, we examined syntactic encoding while patients and matched controls overtly described scenes of moving objects using either separate words (minimal syntactic planning) or sentences (sentence-level syntactic planning). The design of the paradigm also allowed tapping into local noun phrase- and more global sentence-level syntactic planning. Simultaneously, we recorded event-related potentials (ERPs). The patients needed more time to prepare and finish the utterances and made more errors. The patient ERPs had a very similar morphology to that of healthy controls, indicating overall comparable neural processing. Most importantly, the ERPs diverged from those of controls in several functionally informative time windows, ranging from very early (90–150 ms post scene onset) to relatively late (1820–2020 ms post scene onset). These time windows can be associated with different linguistic encoding stages. The ERP results form the first neuroscientific evidence for language production impairments in patients with galactosemia in lexical and syntactic planning stages, i.e., prior to the linguistic output phase. These findings hence shed new light on the language impairments in this disease.     

Advantages of 2'-O-methyl oligoribonucleotide probes for detecting RNA targets.

We have compared various kinetic and melting properties of oligoribonucleotide probes containing 2'-O-methylnucleotides or 2'-deoxynucleotides with regard to their use in assays for the detection of nucleic acid targets. 2'-O-Methyl oligoribonucleotide probes bound to RNA targets faster and with much higher melting temperatures (Tm values) than corresponding 2'-deoxy oligoribonucleotide probes at all lengths tested (8-26 bases). Tm values of both probes increased with length up to approximately 19 bases, with maximal differences in Tm between 2'-O-methyl and 2'-deoxy oligoribonucleotide probes observed at lengths of 16 bases or less. In contrast to RNA targets, 2'-O-methyl oligoribonucleotide probes bound more slowly and with the same Tm to DNA targets as corresponding 2'-deoxy oligoribonucleotide probes. Because of their greatly enhanced Tm when bound to RNA, 2'-O-methyl oligoribonucleotide probes can efficiently bind to double-stranded regions of structured RNA molecules. A 17 base 2'-O-methyl oligoribonucleotide probe was able to bind a double-stranded region of rRNA whereas the same 17 base 2'- deoxy oligoribonucleotide probe did not. Due to their enhanced Tm when bound to RNA targets, shorter 2'-O-methyl oligoribonucleotide probes can be used in assays in place of longer 2'-deoxy oligoribonucleotide probes, resulting in enhanced discrimination between matched and mismatched RNA targets. A 12 base 2'-O-methyl oligoribonucleotide probe had the same Tm as a 19 base 2'-deoxy oligoribonucleotide probe when bound to a matched RNA target but exhibited a much larger decrease in Tm than the 2'-deoxy oligoribonucleotide probe when bound to an RNA target containing either 1 or 2 mismatched bases. The increased Tm, faster kinetics of hybridization, ability to bind to structured targets and increased specificity of 2'-O-methyl oligoribonucleotide probes render them superior to corresponding 2'-deoxy oligoribonucleotides for use in assays that detect RNA targets.     

An Electrochemical Assay of β-1,3-Glucanase Gene from Transgenic Capsicum Using Asymmetric PCR

5′-Thiol-derivatized specific DNA probes were added to the single primer polymerase chain reaction (asymmetric PCR) solution. In the PCR process, the DNA probes extended in the presence of target; the extended probes were then immobilized on a glassy carbon electrode (GCE) via gold nanoparticles. Finally, methylene blue and the extended probes were combined and the electrochemical signals were measured. This signal was higher than that of the GCE modified only by the original probe. When there was no target in PCR solution, the probe did not extend and the signal did not increase. The specific sequences of the β-1,3-glucanase gene were detected successfully from three targets with different length: oligonucleotide, molecule clone vector DNA, and total genome DNA of transgenic capsicum. The detection limits of 2.6 × 10^?13, 7.8 × 10^?13, and 9.1 × 10^?13 moll^?1 for oligonucleotide, molecule clone vector DNA, and total transgenic capsicum genome DNA were estimated.     

Attention in natural scenes: contrast affects rapid visual processing and fixations alike

For natural scenes, attention is frequently quantified either by performance during rapid presentation or by gaze allocation during prolonged viewing. Both paradigms operate on different time scales, and tap into covert and overt attention, respectively. To compare these, we ask some observers to detect targets (animals/vehicles) in rapid sequences, and others to freely view the same target images for 3 s, while their gaze is tracked. In some stimuli, the target''s contrast is modified (increased/decreased) and its background modified either in the same or in the opposite way. We find that increasing target contrast relative to the background increases fixations and detection alike, whereas decreasing target contrast and simultaneously increasing background contrast has little effect. Contrast increase for the whole image (target + background) improves detection, decrease worsens detection, whereas fixation probability remains unaffected by whole-image modifications. Object-unrelated local increase or decrease of contrast attracts gaze, but less than actual objects, supporting a precedence of objects over low-level features. Detection and fixation probability are correlated: the more likely a target is detected in one paradigm, the more likely it is fixated in the other. Hence, the link between overt and covert attention, which has been established in simple stimuli, transfers to more naturalistic scenarios.     

Brain activity in an awake chimpanzee in response to the sound of her own name

The brain activity of a fully awake chimpanzee being presented with her name was investigated. Event-related potentials (ERPs) were measured for each of the following auditory stimuli: the vocal sound of the subject''s own name (SON), the vocal sound of a familiar name of another group member, the vocal sound of an unfamiliar name and a non-vocal sound. Some differences in ERP waveforms were detected between kinds of stimuli at latencies at which P3 and Nc components are typically observed in humans. Following stimulus onset, an Nc-like negative shift at approximately 500 ms latency was observed, particularly in response to SON. Such specific ERP patterns suggest that the chimpanzee processes her name differently from other sounds.     

Brain/behaviour dissociation on old/new distinction in a patient with amnesic syndrome

Event-related potentials (ERP) were recorded in a recognition memory task in 5 healthy subjects and an amnesic patient. A list of high-imagery words with low probability in everyday language was presented visually for 200 ms each. A second list, consisting of 50% previously presented (`old') words and 50% `new' words was presented immediately after the first list. Old/new distinction was determined by the subject's motor response. For each subject single trial analysis of ERPs was performed. In each healthy subjects, correct old/new distinction was associated with significant ERP differences from 500 to 900 ms after stimulus onset. It was, therefore, assumed that task and recording procedures were appropriate for the study of ERPs with recognition memory. The main finding is a dissociation between brain activity and behaviour with old/new distinction in the patient with amnesic syndrome. Frequently, the patient incorrectly classified previously shown words (`old' words) to be presented for the first time (`new'). But ERP showed that brain processing of `old' words which had incorrectly been classified to be `new' is different from correctly classified new words. ERP differences were significant between 900 and 1200 ms after stimulus presentation. These data indicate preserved memory functions which are not assessed at the behavioural level in the memory recognition task.     

Electrophysiological correlates of strategic monitoring in event-based and time-based prospective memory

Prospective memory (PM) is the ability to remember to accomplish an action when a particular event occurs (i.e., event-based PM), or at a specific time (i.e., time-based PM) while performing an ongoing activity. Strategic Monitoring is one of the basic cognitive functions supporting PM tasks, and involves two mechanisms: a retrieval mode, which consists of maintaining active the intention in memory; and target checking, engaged for verifying the presence of the PM cue in the environment. The present study is aimed at providing the first evidence of event-related potentials (ERPs) associated with time-based PM, and at examining differences and commonalities in the ERPs related to Strategic Monitoring mechanisms between event- and time-based PM tasks.The addition of an event-based or a time-based PM task to an ongoing activity led to a similar sustained positive modulation of the ERPs in the ongoing trials, mainly expressed over prefrontal and frontal regions. This modulation might index the retrieval mode mechanism, similarly engaged in the two PM tasks. On the other hand, two further ERP modulations were shown specifically in an event-based PM task. An increased positivity was shown at 400-600 ms post-stimulus over occipital and parietal regions, and might be related to target checking. Moreover, an early modulation at 130-180 ms post-stimulus seems to reflect the recruitment of attentional resources for being ready to respond to the event-based PM cue. This latter modulation suggests the existence of a third mechanism specific for the event-based PM; that is, the "readiness mode".     

Event-related potentials to conjunctions of spatial frequency and orientation as a function of stimulus parameters and response requirements

ERPs were recorded from subjects who were required to push a button in response to a given conjunction of spatial frequency and orientation (target), and to ignore conjunctions sharing with the target only frequency (frequency-relevant), only orientation (orientation-relevant), or neither (irrelevant). Differences between ERPs to irrelevant and frequency-relevant stimuli were identified as frontal selection positivity (Fz, 150–200 msec post-stimulus), selection negativity (Oz, just after 200 msec), and vertex N2b (200–250 msec). For relevant orientations, the selection negativity and the N2b were also found, but the frontal selection positivity was elicited only when the spatial frequency was relevant as well. Neither of these 3 waves was sensitive to spatial frequency or orientation per se. Other waves (N80, N180) did show such sensitivity, but this was independent of stimulus relevance. Hence, direct evidence for the neural-specificity theory, stating that task-related selective ERP responses reflect differential enhancement of activity in stimulus-specific pathways, was not obtained. It is further concluded that ERPs associated with selection of frequency and orientation are highly comparable to those associated with other visual dimensions (e.g., color), and that selection of multiple visual dimensions may be hierarchical at one level of processing and independent at another.     

Mismatch and G-Stack Modulated Probe Signals on SNP Microarrays

Background

Single nucleotide polymorphism (SNP) arrays are important tools widely used for genotyping and copy number estimation. This technology utilizes the specific affinity of fragmented DNA for binding to surface-attached oligonucleotide DNA probes. We analyze the variability of the probe signals of Affymetrix GeneChip SNP arrays as a function of the probe sequence to identify relevant sequence motifs which potentially cause systematic biases of genotyping and copy number estimates.

Methodology/Principal Findings

The probe design of GeneChip SNP arrays enables us to disentangle different sources of intensity modulations such as the number of mismatches per duplex, matched and mismatched base pairings including nearest and next-nearest neighbors and their position along the probe sequence. The effect of probe sequence was estimated in terms of triple-motifs with central matches and mismatches which include all 256 combinations of possible base pairings. The probe/target interactions on the chip can be decomposed into nearest neighbor contributions which correlate well with free energy terms of DNA/DNA-interactions in solution. The effect of mismatches is about twice as large as that of canonical pairings. Runs of guanines (G) and the particular type of mismatched pairings formed in cross-allelic probe/target duplexes constitute sources of systematic biases of the probe signals with consequences for genotyping and copy number estimates. The poly-G effect seems to be related to the crowded arrangement of probes which facilitates complex formation of neighboring probes with at minimum three adjacent G''s in their sequence.

Conclusions

The applied method of “triple-averaging” represents a model-free approach to estimate the mean intensity contributions of different sequence motifs which can be applied in calibration algorithms to correct signal values for sequence effects. Rules for appropriate sequence corrections are suggested.